Eighty percent of G-protein coupled receptors (GPCRs) have a C-terminal consensus sequence for post-translational modification by the addition of a 16-carbon palmitoyl group. This observation strongly suggests that palmitoylation plays an important role in receptor function. The long-term objective of the proposed study is to define the role of palmitoylation in G protein-coupled receptor signaling. The specific aims of this proposal are to: 1) produce knock-in transgenic mice defective for rhodopsin palmitoylation; and 2) phenotypically characterize homozygous knock-in mice. Changes in retinal morphology and visual function will be assessed using a combination of histological, electrophysiological, and biochemical methods. A detailed understanding of rhodopsin structure/function relationships is essential for elucidating the cellular mechanisms by which more than 80 different rhodopsin mutations cause the group of human retinal degenerations collectively referred to as retinitis pigmentosa (RP).